Bacterial Platforms Can Rival Mammalian Platforms

While the COVID-19 pandemic rages, biopharma companies are scaling back nonessential research. However, they are sustaining essential research, including research performed with the assistance of valued partners. One such partner is a synthetic biology company called AbSci. It designs cell expression systems that are tailored to proteins of interest.

AbSci asserts that it has developed technology that can be used to create high-titer cell lines in half the time and a quarter of the cost of traditional expression systems. This technology, SoluPro™, interests AbSci’s partners because it can help them bring biotherapeutics to market more quickly and economically. SoluPro is an engineered Escherichia coli platform that can produce robust, easy-to-work-with expression systems.

“Many next-generation protein therapeutics can’t be produced in other expression systems,” says Sean McClain, AbSci’s founder and CEO. “Often, companies come to us when they’ve tried everything else—mammalian, yeast, traditional E. coli expression systems—unsuccessfully. About 90% of our partnerships fall into this camp.”

McClain and his colleagues don’t accept the term “impossible.” Instead, they’d rather generate ideas to help cell line development break away from longstanding technical and biological constraints. These ideas don’t always work, but when they do, the impossible becomes possible—or even practical.

E. coli platforms can perform like mammalian platforms

SoluPro is a heavily engineered E. coli cell line for biologics manufacturing that incorporates a semi-oxidizing cytoplasm and a dual inducible promoter system that supports precise control of protein production rates. According to AbSci, SoluPro could benefit biomanufacturers specializing in monoclonal antibodies, antibody fragments, and next-generation biologics used in immuno-oncology and many other applications.

“Every protein behaves slightly differently, and we’ve identified the key variables that are important to making soluble protein in E. coli,” McClain points out. “For each project, we build an expression library of more than 10 million unique strains and screen them in proprietary high-throughput assays.” With that, scientists can select strains based on quality and production capability.

“This lets us perform a single experiment to find the right solutions to make a specific protein,” McClain continues. Once the cell line is modified and scalable, and the fermentation process is developed, AbSci licenses the technology to its pharmaceutical client.

Pushing back boundaries

AbSci’s ability to make the theoretical practical is the result of its team’s willingness to defy industry assumptions. “I really encourage all our scientists—and everybody here—to push the bounds of what they think is possible,” McClain insists. “Nobody, anywhere, truly understands everything about biology.

“At AbSci, we try to test whether previous reports or assumptions are accurate. Oftentimes, we find that what the industry and literature said wasn’t possible, is possible. So, we test each hypothesis, rather than discounting them based on previous reports. That’s how you create innovation and grow a good company.”

Persuasion + perseverance = success

McClain founded AbSci nearly nine years ago, as an undergrad at the University of Arizona. “I became obsessed with the biopharma industry and synthetic biology,” he recalls. “I saw how biopharma started with E. coli expression systems to manufacture insulin, and then shifted to mammalian cells for complex antibodies. I wanted to use synthetic biology to make E. coli more ‘mammalian like,’ so it could produce soluble antibodies.”

With that idea, he graduated early, moved home with his parents, and bootstrapped the company. He even convinced his fiancé to move into his parents’ home and dedicate her salary to supporting the company. Within 18 months, he had proof of concept. He had made full-length soluble antibodies in E. coli.

“During that time,” he relates, “I reached out to large pharmas, asking for guidance on industry needs for cell line characteristics. Two responded, and one gave me some helpful specs. I used that to build the initial platform.”

Then he reached out again. “One of the large pharma companies gave us five molecules and their desired production targets,” he remembers. “We achieved every single one. The company said no one had ever been successful with all five molecules before.” Since then, AbSci has raised around $40 million.

The company went commercial in 2018, getting market traction and building revenue. McClain reports that for 2019, revenue grew about 800%. He expects that for 2020, revenues will triple. “We just doubled our facility size to about 12,000 square feet to meet market demand,” he adds.

The company also recently announced an exclusive co-marketing agreement in which the contract development and manufacturing organization KBI Biopharma will market AbSci’s Protein Printing™ technology globally for the industrial scale-up of biologics manufacturing. That technology is the combination of AbSci’s SoluPro expression platform, its advanced synthetic biology strain engineering capability, and its proprietary high-throughput screening assays.

“We’re generating tens of millions of data points for protein production and folding, and we are mining that data using machine learning,” McClain says. “We want to be able to predict titer based on amino acid sequences.” By building what may be the world’s largest searchable database for protein expression and folding, AbSci is one step closer to becoming what McClain calls “the Google of synthetic biology.”

Gold-standard goal

When addressing a large problem, an entrepreneur will break it into subproblems that can be solved serially. For the entrepreneurial McClain, the current subproblem is how to effectively scale the company.

With a backlog of projects, McClain is working to execute on existing projects effectively and in appropriate timeframes, as well as to quickly hire the right employees. Based in Vancouver, WA—not a biotech hotbed—AbSci is attracting biotech expertise from hubs in Seattle, San Francisco, San Diego, and Boston.

“We want to be the gold standard for cell lines making next-generation biologics,” McClain declares. To reach that point, AbSci needs to establish itself more firmly in the biopharma space. Afterward, McClain plans to expand into industrial, agricultural, and food verticals. “It’s really important for us to establish ourselves and stay focused in one industry, for now,” he stresses. “Once we win one market, it’s easier to replicate that success in another.”

There are technical limitations to overcome, however. “We’re unable to glycosylate proteins,” McClain admits. Glycosylation is a company priority even though demand for glycosylation is low for next-generation antibodies. “To be the gold standard,” he maintains, “we need to incorporate that capability.”

To achieve the future it envisions, AbSci must keep challenging itself, continually pushing biology’s boundaries. But that’s not impossible. That’s in its DNA.